Oral pharmaceutical dosage forms of budesonide

Abstract

The present invention relates to novel oral sustained release pharmaceutical dosage forms for delivery of budesonide to the lower gastrointestinal tract for the treatment of Crohn's disease.

We claim: 
     
       1. A sustained release pharmaceutical dosage form in the form of a capsule, sachet or pouch, comprising:
 a) an inert core, 
 b) a first sustained release sugar matrix layer surrounding the inert core, the sugar matrix layer comprising budesonide, a water insoluble polymer and sugar, wherein the ratio of sugar to water insoluble polymer is greater than 3:1; and 
 c) a second delayed release film coating surrounding the sustained release sugar matrix layer, wherein, the sustained release pharmaceutical dosage form when tested for dissolution in a USP Apparatus II at 75 rpm in 1000 ml of 0.1 N HCl for 2 hours followed by a change to pH 5.5 buffer, exhibits the following dissolution profile 
 a) less than 5% of total budesonide is released after 2 hours; 
 b) from about 5% to about 15% of total budesonide is released after 3 hours; 
 c) from about 15% to about 20% of total budesonide is released after 4 hours; 
 d) from about 30% to about 40% of total budesonide is released after 6 hours; 
 e) from about 40% to about 50% of total budesonide is released after 8 hours; 
 f) not less than 50% of total budesonide is released after 10 hours. 
 
     
     
       2. A sustained release pharmaceutical dosage form as in  claim 1 , wherein the water insoluble polymer is ethyl cellulose. 
     
     
       3. A sustained release pharmaceutical dosage form as in  claim 1 , wherein the sugar matrix layer comprises sugar in an amount from about 50 to about 80% of the total weight of sugar matrix layer. 
     
     
       4. A sustained release pharmaceutical dosage form as in  claim 1 , wherein the water insoluble polymer is present in an amount from about 5 to about 15% of the total weight of the sugar matrix layer. 
     
     
       5. A sustained release pharmaceutical dosage form of  claim 1 , wherein delayed release film coating comprises copolymers of acrylic acid and methacrylic acid esters. 
     
     
       6. A sustained release pharmaceutical dosage form of  claim 1 , wherein the amount of budesonide is in the range of from about 6mg to about 9mg. 
     
     
       7. A sustained release pharmaceutical dosage form of  claim 1 , wherein budesonide is present in an amount from about 15% to about 25% of the total weight of the sugar matrix layer. 
     
     
       8. A sustained release pharmaceutical dosage form of  claim 1 , wherein budesonide is present in an amount from about 1.5% to about 3.5% of the total weight of sustained release pharmaceutical dosage form. 
     
     
       9. A sustained release pharmaceutical dosage form of  claim 1 , for use in the treatment of Crohn's disease. 
     
     
       10. A sustained release pharmaceutical dosage form of  claim 1 , for use in the maintenance of clinical remission of mild to moderate Crohn's disease involving the ileum and/or the ascending colon. 
     
     
       11. A sustained release dosage form in the form of a capsule, sachet or pouch comprising:
 a) an inert core, 
 b) a first sustained release sugar matrix layer surrounding the inert core, the sugar matrix layer comprising budesonide, a water insoluble polymer and sugar, wherein the ratio of sugar to water insoluble polymer is greater than 3:1; and 
 c) a second delayed release film coating surrounding the sustained release sugar matrix layer, the sustained release pharmaceutical dosage form when tested for dissolution in a USP Apparatus II at 75 rpm in 1000 ml of 0.1 N HCl for 2 hours followed by a change to pH 5.5 buffer, exhibiting the following dissolution profile 
 a) less than 5% of total budesonide is released after 2 hours; 
 b) from about 5% to about 15% of total budesonide is released after 3 hours; 
 c) from about 15% to about 20% of total budesonide is released after 4 hours; 
 d) from about 30% to about 40% of total budesonide is released after 6 hours; 
 e) from about 40% to about 50% of total budesonide is released after 8 hours; 
 f) not less than 50% of total budesonide is released after 10 hours; and 
 when tested for dissolution in a USP Apparatus II at 75 rpm in 1000 ml of 0.1 N HCl for 2 hours followed by a change to pH 7.5 buffer, exhibits the following dissolution profile, 
 a) less than 5% of total budesonide is released after 2 hours; 
 b) from about 30% to about 50% of total budesonide is released after 3 hours; 
 c) from about 40% to about 60% of total budesonide is released after 4 hours; 
 d) from about 65% to about 85% of total budesonide is released after 6 hours; 
 e) not less than 80% of total budesonide is released after 8 hours. 
 
     
     
       12. A sustained release pharmaceutical dosage form of  claim 11 , for use in the treatment of Crohn's disease. 
     
     
       13. A sustained release pharmaceutical dosage form of  claim 11 , for use in the maintenance of clinical remission of mild to moderate Crohn's disease involving the ileum and/or the ascending colon. 
     
     
       14. A sustained release pharmaceutical dosage form as in  claim 11 , wherein the sugar matrix layer comprises sugar in an amount from about 50 to about 80% of the total weight of sugar matrix layer, and the water insoluble polymer is present in an amount from about 5 to about 15% of the total weight of the sugar matrix layer. 
     
     
       15. A sustained release pharmaceutical dosage form of  claim 11 , wherein delayed release film coating comprises copolymers of acrylic acid and methacrylic acid esters.